Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Most patients suffering from breast carcinoma do not die due to the primary tumor but from the development of metastases. Active migration of cancer cells is a prerequisite for development of these metastases. We used time-lapse videomicroscopy and computer-assisted cell tracking of MDA-MB-468 human breast carcinoma cells, which were incorporated into a three-dimensional collagen matrix, in order to analyze the migratory activity of these cells in response to different neurotransmitters. Our results show that met-enkephalin, substance P, bombesin, dopamine, and norepinephrine have a stimulatory effect on the migration of the breast cancer cells; moreover, these cells show positive chemotaxis towards norepinephrine as was analyzed by the directionality and persistence on a single-cell basis. Gamma-aminobutyric acid (GABA) however has an inhibitory effect. Endorphin and leu-enkephalin, as well as histamin and acetylcholine, had no influence on the migratory activity of the cells. In summary, we provide evidence for a strong regulatory involvement of neurotransmitters in the regulation of breast cancer cell migration, which might provide the basis for the use of the pharmacological agonists and antagonists for the chemopreventive inhibition of metastasis development.
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PMID:Effects of neurotransmitters on the chemokinesis and chemotaxis of MDA-MB-468 human breast carcinoma cells. 1288 99

Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter, and GABA receptors have been recently detected on epithelial colon cancer cells. Nembutal (pentobarbital) is a barbiturate with GABA-agonistic effects. We demonstrate that GABA receptors are present on colon cancer cell lines (KM12SM, HT29, RKO). Nembutal (0.1-500 microg/ml) continuous exposure resulted in an IC50 level of 58 microg/ml for the KM12SM cells and 120 microg/ml for the HT29 cells. Nembutal reduced cellular cAMP concentration in colon cancer cells and resulted in a dose and time dependent decrease in MMP-2 and MMP-9 levels. In the KM12SM intracecal injected mice, 9 of 10 mice in the metaphane group developed a primary tumor (mean weight = 2.16 g +/- 0.76) compared to 7 of 10 mice in the nembutal group (mean weight = 0.41 g +/- 0.21, p = 0.03). In the KM12SM intrasplenic injected mice, the tumor weight in the spleen was 85% smaller in the nembutal group compared to the metaphane group (p = 0.008). In the HT29 injected mice, the metaphane group and nembutal group had similar tumor incidence, but combined tumor weight (primary tumor and liver metastases) was significantly higher in the metaphane group (1.61+/- 0.45 g) versus 0.07 +/- 0.05 g; p = 0.008. The incidence of liver metastases in the nembutal group was zero compared to eight out of nine in the metaphane group. To the best of our knowledge, this is the first evidence that nembutal is a potent inhibitor of primary colon cancer and metastasis. These findings may have therapeutic implications for the treatment of colon and other cancers.
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PMID:Inhibition of experimental colon cancer metastasis by the GABA-receptor agonist nembutal. 1597 Jul 6